Photodynamic therapy (abbreviated as PDT), also known as photoradiation therapy (abbreviated as PRT) or also known as photochemotherapy, is a treatment method on the basis of the photochemical reaction principle of specific chemical substances. The chemical substance used therein is referred to as a chemical diagnosis and treatment drug for tumor (also known as a photosensitizer, abbreviated as PS). The PDT process lies in that a photosensitizer is intravenously injected into the body (for the skin, it can also be applied to the affected area), and after a certain time the tumor tissue is irradiated with a specific wavelength of light, the photosensitizer enriched in the tumor tissue under the excitation of light generates a series of photophysical chemical reactions and generates cytotoxic reactive oxygen species, thereby killing the cancer cells to destroy the tumor tissue.
This therapy was approved by the US FDA for clinical use in 1996, and listed as one of the five basic methods for tumor treatment (surgery, radiotherapy, chemotherapy, photodynamic therapy, biochemical immunology) by FDA in 1997. Compared with traditional therapies, the PDT has the advantages of small trauma, low toxicity, good selectivity, good applicability, repeatable treatment, palliative treatment, and can be combined with a surgery to improve the efficacy, can eliminate the occult cancerous lesions, can protect the appearance and vital organ function, and the treatment time is short, etc.
The photodynamic therapy may also be effective in treating non-cancer diseases such as bacterial infections, oral infections, eye diseases of macular degeneration, atherosclerosis, wound infections, and skin diseases etc. The photosensitizer can also be used for photodynamic disinfection, most importantly for the sterilization and disinfection of blood and blood derivatives. Meanwhile, the fluorescence property of the photosensitizer can be used for photodynamic diagnosis, which is also an important use of the medical photosensitizer.
Photosensitizer is the key of the photodynamic therapy and the photodynamic effect depends on the good or bad photosensitizer. Based on the potential of the photodynamic therapy in the treatment of cancers and other diseases, it is generally believed in the scientific field that the photodynamic therapy will become an important method of medical treatment in the 21st century. The main clinical photosensitizer used currently is porfimer sodium, the first generation of photosensitizer. In 1993, Photofrin II is officially put into production by Quadra Logic Technologies Phototherapeutics Inc (Canadian), and the trade name is porfimer sodium. The drug went on sale in Netherland (1994), Canada (1995), Japan (1996), United States (1996), France (1997), Germany (1997), the United Kingdom (2001), Israel (2002), Portugal (2002), Greece (2003) and the like successively.
Although porfimer sodium achieved clinical success, but its components are complicated, the effects of various components in photodynamic injury have also not been made clear; the inactive ingredients accounting for more than 20% of the total drug not only failed to produce effective photodynamic injury to the lesion target tissue but became a culprit resulting in photosensitivity reactions in normal tissues. Therefore, the tissue selectivity and stability of the photodynamic damage strength of first generation of photosensitizers are very poor, the skin phototoxicity is strong, and the time away from light is long (after the treatment, the patients must be strictly protected from light for 4-6 weeks). In addition, there is a very weak absorption band in the absorption spectrum of a mixed porphyrin photosensitizer at the treatment wavelength of 630 nm, such a photosensitizer cannot absorb the red light part well, and the treatment depth is not enough (about 2 mm), which also affects its clinical efficacy. Although these deficiencies did not prevent porfimer sodium from becoming a useful drug for anti-cancers and other diseases, the exploration of the second generation of photosensitizer having better physical, chemical and spectral properties becomes more meaningful.
The phthalocyanine complex as a photosensitizer in the PDT treatment is better than porfimer sodium in clinical use, and its advantages can be summarized as follows: 1) its structure is clear, and its properties are stable. It has a large conjugated system, a clear structure, and stable properties. Also, the central ion, axial ligands, type and number of substituents on the rings can be changed as required to synthesize a desired drug, and there are great alternatives; 2) the preparation is relatively easy, and the cost is lower; 3) there is an optimal effect wavelength and stronger penetration to the tissue. The phthalocyanine complex generally has a maximum absorption wavelength of between 660-700 nm, its absorption to the light of a wavelength of 680 nm is 10-50 times stronger than porfimer sodium, and the ability to penetrate the skin tissue of the 680 nm light increased by 20% than that of the 630 nm light, and the ability to penetrate brain tissue increased by 50%, so the phthalocyanine complex is more suitable for the treatment of deep tissue cancers than porfimer sodium; 4) the dark toxicity is low, and the skin phototoxicity is low. Although there are many phthalocyanine complexes which have been studied as photosensitizers, there are no phthalocyanine photosensitizers saled in the market. Therefore, the second generation of phthalocyanine photosensitive drug having high activity and low toxicity is the recent research focus.